Project Summary Our studies will assess if donor skeletal muscle tissue (from human cadavers and mice) transplanted into host muscle through a novel Minimally Invasive Muscle Embedding (MIME) technique can promote donor-derived myogenesis. Our studies will also assess in neuromuscular electrical stimulation and forceful eccentric muscle contractions can enhance donor-derived myogenesis. We will perform our studies in immunodeficient NSG- GFP mice, which are not only good hosts for transplantation studies due to the low risk of immune rejection, but also because they express a green fluorescent protein (GFP) reporter in all their cells, making it easy to differentiate between host (GFP(+)) and donor-derived (GFP(-)) muscle fibers. We will assess donor-derived myogenesis through histological studies as well as physiological studies. If successful, our studies could have significant translational impact in the treatment of muscle loss arising from muscle disease and trauma. Our studies could also pave the way for a new line of research looking into the use of cadaveric muscle as a source of myogenic cells; provide important insights into the kinds of muscle activity needed to increase myogenesis from bioengineered muscle containing myogenic cells; and, also help in the development of animal models of human muscle disease where transplantation of human muscle into mouse is the approach of choice.